High Antibody-Dependent Cellular Cytotoxicity Antibody Titers to H5N1 and H7N9 Avian Influenza A Viruses in Healthy US Adults and Older Children
| dc.contributor.author | Terajima, Masanori | |
| dc.contributor.author | Co, Mary Dawn T. | |
| dc.contributor.author | Cruz, John | |
| dc.contributor.author | Ennis, Francis A. | |
| dc.date | 2022-08-11T08:09:09.000 | |
| dc.date.accessioned | 2022-08-23T16:19:17Z | |
| dc.date.available | 2022-08-23T16:19:17Z | |
| dc.date.issued | 2015-10-01 | |
| dc.date.submitted | 2017-08-04 | |
| dc.identifier.citation | J Infect Dis. 2015 Oct 1;212(7):1052-60. doi: 10.1093/infdis/jiv181. Epub 2015 Mar 20. <a href="https://doi.org/10.1093/infdis/jiv181">Link to article on publisher's site</a> | |
| dc.identifier.issn | 0022-1899 (Linking) | |
| dc.identifier.doi | 10.1093/infdis/jiv181 | |
| dc.identifier.pmid | 25795791 | |
| dc.identifier.uri | http://hdl.handle.net/20.500.14038/35009 | |
| dc.description.abstract | Human influenza is a highly contagious acute respiratory illness that is responsible for significant morbidity and excess mortality worldwide. In addition to neutralizing antibodies, there are antibodies that bind to influenza virus-infected cells and mediate lysis of the infected cells by natural killer (NK) cells (antibody-dependent cellular cytotoxicity [ADCC]) or complement (complement-dependent lysis [CDL]). We analyzed sera obtained from 16 healthy adults (18-63 years of age), 52 children (2-17 years of age), and 10 infants (0.75-1 year of age) in the United States, who were unlikely to have been exposed to the avian H7N9 subtype of influenza A virus, by ADCC and CDL assays. As expected, none of these sera had detectable levels of hemagglutination-inhibiting antibodies against the H7N9 virus, but we unexpectedly found high titers of ADCC antibodies to the H7N9 subtype virus in all sera from adults and children aged > /=8 years. | |
| dc.language.iso | en_US | |
| dc.relation | <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=25795791&dopt=Abstract">Link to Article in PubMed</a> | |
| dc.relation.url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4668882/ | |
| dc.subject | ADCC | |
| dc.subject | complement-dependent lysis | |
| dc.subject | H7N9 subtype | |
| dc.subject | H5N1 subtype | |
| dc.subject | antibody-dependent cell-mediated cytotoxicity | |
| dc.subject | antibody-dependent cellular cytotoxicity | |
| dc.subject | avian influenza viruses | |
| dc.subject | hemagglutination-inhibition | |
| dc.subject | non-neutralizing antibody | |
| dc.subject | Immunity | |
| dc.subject | Immunology and Infectious Disease | |
| dc.subject | Immunology of Infectious Disease | |
| dc.subject | Infectious Disease | |
| dc.title | High Antibody-Dependent Cellular Cytotoxicity Antibody Titers to H5N1 and H7N9 Avian Influenza A Viruses in Healthy US Adults and Older Children | |
| dc.type | Journal Article | |
| dc.source.journaltitle | The Journal of infectious diseases | |
| dc.source.volume | 212 | |
| dc.source.issue | 7 | |
| dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/infdis_pp/227 | |
| dc.identifier.contextkey | 10542738 | |
| html.description.abstract | <p>Human influenza is a highly contagious acute respiratory illness that is responsible for significant morbidity and excess mortality worldwide. In addition to neutralizing antibodies, there are antibodies that bind to influenza virus-infected cells and mediate lysis of the infected cells by natural killer (NK) cells (antibody-dependent cellular cytotoxicity [ADCC]) or complement (complement-dependent lysis [CDL]). We analyzed sera obtained from 16 healthy adults (18-63 years of age), 52 children (2-17 years of age), and 10 infants (0.75-1 year of age) in the United States, who were unlikely to have been exposed to the avian H7N9 subtype of influenza A virus, by ADCC and CDL assays. As expected, none of these sera had detectable levels of hemagglutination-inhibiting antibodies against the H7N9 virus, but we unexpectedly found high titers of ADCC antibodies to the H7N9 subtype virus in all sera from adults and children aged > /=8 years.</p> | |
| dc.identifier.submissionpath | infdis_pp/227 | |
| dc.contributor.department | Division of Infectious Diseases and Immunology, Department of Medicine | |
| dc.source.pages | 1052-60 |
This item appears in the following Collection(s)
Related items
Showing items related by title, author, creator and subject.
-
Therapeutic Antibody Against Neisseria gonorrhoeae Lipooligosaccharide, a Phase-variable Virulence FactorNeisseria gonorrhoeae (Ng) which causes gonorrhea has become multidrug-resistant, necessitating the development of novel therapeutics and vaccines. mAb 2C7 which targets an epitope within an important virulence factor, the lipooligosaccharide (LOS), is a candidate therapeutic mAb. Ninety-four percent of clinical isolates express the 2C7-epitope which is also a vaccine target. Ng expresses multiple LOS(s) due to phase-variation (pv) of LOS glycosyltransferase (lgt) genes. mAb 2C7 reactivity requires a lactose extension from the LOS core Heptose (Hep) II (i.e. lgtG ‘ON’ [G+]). Pv results in HepI with: two (2-), three (3-), four (4-), or five (5-) hexoses (Hex). How HepI glycans impact Ng infectivity and mAb 2C7 function are unknown and form the bases of this dissertation. Using isogenic mutants, I demonstrate that HepI LOS glycans modulate mAb 2C7 binding. mAb 2C7 causes complement (C’)-dependent bacteriolysis of three (2-Hex/G+, 4-Hex/G+, and 5-Hex/G+) of the HepI mutants in vitro. The 3-Hex/G+ mutant (resistant to C’-dependent bacteriolysis) is killed by neutrophils in the presence of mAb and C’. In mice, 2- and 3-Hex/G+ infections are significantly shorter than 4- and 5-Hex/G+ infections. A chimeric mAb 2C7 that hyperactivates C’, attenuates only 4- and 5-Hex/G+ infections. This study enhances understanding of the role of HepI LOS pv in gonococcal infections and shows that longer HepI glycans are necessary for prolonged infections in vivo. This is the first study that predicts in vitro efficacy of mAb 2C7 against all four targetable HepI glycans thereby strengthening the rationale for development of 2C7-epitope based vaccines and therapeutics.
-
Immunofluorescence imaging of DNA damage response proteins: optimizing protocols for super-resolution microscopy.Immunofluorescence imaging has provided captivating visual evidence for numerous cellular events, from vesicular trafficking, organelle maturation and cell division to nuclear processes including the appearance of various proteins and chromatin components in distinct foci in response to DNA damaging agents. With the advent of new super-resolution microscope technologies such as 4Pi microscopy, standard immunofluorescence protocols deserve some reevaluation in order to take full advantage of these new technological accomplishments. Here we describe several methodological considerations that will help overcome some of the limitations that may result from the use of currently applied procedures, with particular attention paid to the analysis of possible colocalization of fluorescent signals. We conclude with an example of how application of optimized methods led to a breakthrough in super-resolution imaging of nuclear events occurring in response to DNA damage.
-
Profiles of human serum antibody responses elicited by three leading HIV vaccines focusing on the induction of Env-specific antibodiesIn the current report, we compared the specificities of antibody responses in sera from volunteers enrolled in three US NIH-supported HIV vaccine trials using different immunization regimens. HIV-1 Env-specific binding antibody, neutralizing antibody, antibody-dependent cell-mediated cytotoxicity (ADCC), and profiles of antibody specificity were analyzed for human immune sera collected from vaccinees enrolled in the NIH HIV Vaccine Trial Network (HVTN) Study #041 (recombinant protein alone), HVTN Study #203 (poxviral vector prime-protein boost), and the DP6-001 study (DNA prime-protein boost). Vaccinees from HVTN Study #041 had the highest neutralizing antibody activities against the sensitive virus along with the highest binding antibody responses, particularly those directed toward the V3 loop. DP6-001 sera showed a higher frequency of positive neutralizing antibody activities against more resistant viral isolate with a significantly higher CD4 binding site (CD4bs) antibody response compared to both HVTN studies #041 and #203. No differences were found in CD4-induced (CD4i) antibody responses, ADCC activity, or complement activation by Env-specific antibody among these sera. Given recent renewed interest in realizing the importance of antibody responses for next generation HIV vaccine development, different antibody profiles shown in the current report, based on the analysis of a wide range of antibody parameters, provide critical biomarker information for the selection of HIV vaccines for more advanced human studies and, in particular, those that can elicit antibodies targeting conformational-sensitive and functionally conserved epitopes.
